JPH10182687A - Stabilization of storage of acarbose - Google Patents
Stabilization of storage of acarboseInfo
- Publication number
- JPH10182687A JPH10182687A JP9177833A JP17783397A JPH10182687A JP H10182687 A JPH10182687 A JP H10182687A JP 9177833 A JP9177833 A JP 9177833A JP 17783397 A JP17783397 A JP 17783397A JP H10182687 A JPH10182687 A JP H10182687A
- Authority
- JP
- Japan
- Prior art keywords
- acarbose
- oxygen
- container
- moisture
- containing preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
- C07H3/06—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明はアカルボース又はア
カルボース含有製剤の保存方法に関する。[0001] The present invention relates to a method for storing acarbose or acarbose-containing preparations.
【０００２】[0002]
【背景技術】アカルボースは、放線菌の一種Actinoplan
es属のアミノ糖産生菌の培養液から分離・精製される物
質であり、ヒトの腸管内で炭水化物の消化・吸収に関与
するα−アミラーゼ及びα−グルコシダーゼ（スクラー
ゼ、マルターゼ等）の活性を阻害し、糖質の消化吸収を
遅延させて食後の血糖上昇を抑制する作用を有してお
り、経口糖尿病治療薬として広く使用されている（特公
昭59-18797号公報、特公平7-39340号公報、特公平7-455
37号公報、特許第2,502,551号明細書等参照）。[Background Art] Acarbose is a kind of actinomycete Actinoplan
A substance separated and purified from the culture of amino sugar-producing bacteria of the genus es, which inhibits the activities of α-amylase and α-glucosidase (sucrase, maltase, etc.) involved in the digestion and absorption of carbohydrates in the human intestinal tract It has the effect of delaying the digestion and absorption of carbohydrates and suppressing postprandial rise in blood sugar, and is widely used as a therapeutic drug for oral diabetes (JP-B-59-18797, JP-B-7-39340) Gazette, Tokuhei 7-455
No. 37, Patent No. 2,502,551).
【０００３】アカルボースは、Ｏ−4,6−ジデオキシ−
４−［［（1S,4R,5S,6S）−4,5,6−トリヒドロキシ−３
−（ヒドロキシメチル）−２−シクロヘキセン−１−イ
ル］アミノ］−α−Ｄ−グルコピラノシル−（１→４）
−Ｏ−α−Ｄ−グルコピラノシル−（１→４）−Ｄ−グ
ルコピラノースに対する一般名であり、その性状は白色
ないし淡黄色の粉末である。Acarbose is O-4,6-dideoxy-
4-[[(1S, 4R, 5S, 6S) -4,5,6-trihydroxy-3
-(Hydroxymethyl) -2-cyclohexen-1-yl] amino] -α-D-glucopyranosyl- (1 → 4)
-O-α-D-glucopyranosyl- (1 → 4) -D-glucopyranose is a general name, and is a white to pale yellow powder.
【０００４】アカルボースは吸湿性が強く、水分含量が
アカルボース又はアカルボース含有製剤の貯蔵安定性に
大きく影響を及ぼすことが知られている。 例えば、特
公平７−３９３４０号公報には、アカルボースを含有す
る錠剤の水分含有量が約６重量％を超えると、温度60
℃、6週間の保存中にアカルボースの含量が低下し、変
色をきたすことが記載されている。また、「医学と薬
学、３２巻３号５９７−６０１頁（１９９４年９月）に
は、アカルボースを含有する錠剤を20℃、湿度75％及び
30℃、湿度90％の条件下で4週間保存した結果、成分含
量に変化はないものの、錠剤の重量増加、硬度の低下及
び外観の変化（白色錠剤が淡黄〜淡褐色に変化）が認め
られたことが報告されている。It is known that acarbose is highly hygroscopic, and that the water content greatly affects the storage stability of acarbose or acarbose-containing preparations. For example, Japanese Patent Publication No. Hei 7-39340 discloses that when the water content of acarbose-containing tablets exceeds about 6% by weight, the temperature increases to 60%.
It is described that the content of acarbose decreases during storage for 6 weeks at ℃, resulting in discoloration. Further, "Medical and Pharmacy, Vol. 32, No. 3, pp. 597-601 (September, 1994) states that tablets containing acarbose can be treated at 20 ° C., 75% humidity,
As a result of storage at 30 ° C and 90% humidity for 4 weeks, there is no change in the component content, but tablet weight increase, hardness decrease and appearance change (white tablet changes from pale yellow to pale brown) Has been reported.
【０００５】このため、従来、アカルボース又はアカル
ボース含有製剤の保存にあたっては、乾燥状態に保つこ
とが必要とされ、例えば錠剤の場合、通常広く使用され
るＰＶＣ（ポリ塩化ビニル）製ＰＴＰ包装ではフィルム
を透過する空気中の水分の影響で貯蔵中に錠剤が変色
（白色から淡黄色への変化）し、長期間の貯蔵に耐えな
いため、ＰＴＰ包装の素材として水分透過性のより低い
ＣＰＰ（ポリプロピレン）等が用いられ、これをさらに
アルミラミネートフィルムで密封包装するなどの措置が
とられている。しかしながら、このように厳重に耐湿包
装を施しても、なお貯蔵中に錠剤が若干変色することが
あり、これによって商品価値を損なう虞が有ったが、こ
れまでその原因がわからず、その対策に苦慮していた。[0005] For this reason, conventionally, it is necessary to keep acarbose or acarbose-containing preparations in a dry state when storing them. For example, in the case of tablets, a film is generally used in PTP packaging made of PVC (polyvinyl chloride) which is widely used. CPP (polypropylene) with lower moisture permeability as a material for PTP packaging because tablets discolor (change from white to pale yellow) during storage due to the effect of moisture in the permeating air and do not withstand long-term storage And the like, and measures such as further sealing and packaging the same with an aluminum laminated film are taken. However, even with such strict moisture-resistant packaging, the tablets may still be slightly discolored during storage, which may impair the commercial value of the tablets. Was struggling.
【０００６】本発明者は、貯蔵中のアカルボース又はア
カルボース含有製剤の変色を完全に阻止し、アカルボー
スの品質を長期間安定に保持することのできる方法につ
いて鋭意研究を重ねた結果、意外なことに、アカルボー
ス又はアカルボース含有製剤を、耐湿条件下で且つ実質
的に酸素を含まない雰囲気中に保持すると、アカルボー
ス又はアカルボース含有製剤の変色を完全に防止するこ
とができ、アカルボースの貯蔵安定性が著しく向上する
ことを見出し、本発明を完成するに至った。The present inventor has conducted extensive studies on a method capable of completely preventing discoloration of acarbose or acarbose-containing preparation during storage and maintaining the quality of acarbose stably for a long period of time. When acarbose or an acarbose-containing preparation is kept in a moisture-resistant condition and in an atmosphere substantially free of oxygen, discoloration of the acarbose or the acarbose-containing preparation can be completely prevented, and the storage stability of acarbose is significantly improved. And completed the present invention.
【０００７】[0007]
【発明の開示】かくして、本発明は、アカルボース又は
アカルボース含有製剤を実質的に酸素を含まない雰囲気
中に保持することを特徴とするアカルボース又はアカル
ボース含有製剤の保存方法を提供するものである。Thus, the present invention provides a method for preserving acarbose or an acarbose-containing preparation, which comprises maintaining the acarbose or the acarbose-containing preparation in an atmosphere substantially free of oxygen.
【０００８】ここで「実質的に酸素を含まない雰囲気」
とは、雰囲気中の酸素濃度が１％以下、好ましくは０.
５％以下、より好ましくは０.１％以下である状態の雰
囲気であり、かかる雰囲気は、例えば、金属製容器、ガ
ラスボトル、アルミニウムラミネートフイルム製の袋な
どの実質的に気体不透過性の耐湿容器の内部の空気を窒
素ガス、炭酸ガス等の酸素を実質的に含まない不活性ガ
スと置換するか又は真空にするか、該容器内の空気から
酸素を実質的に除去する等の方法により形成することが
できる。[0008] Here, "atmosphere substantially containing no oxygen"
Means that the oxygen concentration in the atmosphere is 1% or less, preferably 0.1%.
The atmosphere is in a state of 5% or less, more preferably 0.1% or less, and is, for example, a substantially gas-impermeable moisture-resistant material such as a metal container, a glass bottle, and a bag made of an aluminum laminated film. The air inside the container is replaced with an inert gas substantially free of oxygen such as nitrogen gas, carbon dioxide gas or the like, or is evacuated, or oxygen is substantially removed from the air inside the container. Can be formed.
【０００９】該耐湿容器内の空気から酸素を実質的に除
去する最も簡便な方法は、該容器内に脱酸素剤を入れて
密封する方法である。この酸素除去のために使用する脱
酸素剤は、従来から知られている無機系（鉄粉、亜硫酸
塩等）、有機系（カテコール、アスコルビン酸、不飽和
鎖状炭化水素重合物等）のいずれの種類のものでも使用
可能であるが［機能包装実用事典」（株式会社フジ・テ
クノシステム １９９４年８月１日発行）参照］特に、
低湿度下でも酸素を吸収することができるものが好適で
ある。脱酸素剤の形状は、例えば、粉状、粒状、塊状、
シート状等のいずれであってもよく、また、脱酸素剤組
成物を熱可塑性樹脂に分散させたシート状またはフィル
ム状のものであってもよい。また、脱酸素剤は通気性材
料に被覆包装して用いることができ、その形態は、例え
ば、通気性材料に包装された小袋状、通気性材料で被覆
又は積層されたシート状等であることができる。The simplest method of substantially removing oxygen from the air in the moisture-resistant container is a method in which a deoxidizer is placed in the container and the container is sealed. The oxygen scavenger used for removing oxygen may be any of conventionally known inorganic (iron powder, sulfite, etc.) and organic (catechol, ascorbic acid, unsaturated chain hydrocarbon polymer, etc.). However, it is also possible to use the ones of the type described in [Functional Packaging Practical Encyclopedia] (Fuji Techno System Co., Ltd., issued on August 1, 1994)]
Those capable of absorbing oxygen even under low humidity are preferred. The shape of the oxygen scavenger is, for example, powdery, granular, massive,
It may be in the form of a sheet or the like, or may be in the form of a sheet or a film in which the oxygen scavenger composition is dispersed in a thermoplastic resin. In addition, the oxygen absorber can be used by covering and wrapping a gas-permeable material, for example, in the form of a small bag packed with a gas-permeable material, a sheet coated or laminated with a gas-permeable material, or the like. Can be.
【００１０】このような脱酸素剤は市販されており、そ
の一例としては、「エージレス」という名称で販売され
ている三菱ガス化学株式会社製の一連の製品が挙げられ
る。中でも、低水分下で作用する自力反応型のもの、例
えばエージレスＳ、エージレスＺ、エージレスＧ等が好
適に用いられる。[0010] Such oxygen absorbers are commercially available, an example of which is a series of products manufactured by Mitsubishi Gas Chemical Co., Ltd. sold under the name "Ageless". Among them, a self-reaction type acting under low moisture, for example, Ageless S, Ageless Z, Ageless G and the like are suitably used.
【００１１】一方、アカルボースは、前述したとおり吸
湿性があり、水分を吸収して経時的に変化するので、ア
カルボース原末及びアカルボース含有製剤、例えば錠
剤、顆粒剤、散剤等はそれ自体水分を実質的に含まない
（水分含量が約６重量％以下、特に約５重量％以下であ
る）ことが望ましいことは勿論のこと、かかる水分含量
の少ないアカルボース及びアカルボース含有製剤を水分
の少ない雰囲気、通常、相対湿度が２０％以下、好まし
くは１０％以下の乾燥した雰囲気下に保持することも重
要である。On the other hand, as described above, acarbose is hygroscopic and absorbs water, and changes over time. Therefore, acarbose bulk powder and acarbose-containing preparations, such as tablets, granules, powders, etc., themselves substantially absorb water. It is of course desirable not to contain such water (water content is about 6% by weight or less, especially about 5% by weight or less). It is also important to keep in a dry atmosphere with a relative humidity of 20% or less, preferably 10% or less.
【００１２】そのような乾燥した雰囲気は、例えば、前
述した気体不透過性の耐湿容器内に、脱酸素剤と共に、
乾燥剤を入れて密封することにより容器に形成すること
ができる。使用しうる乾燥剤としては、五酸化リン、塩
化カルシウム、シリカゲル、酸化カルシウム等が挙げら
れ、中でもシリカゲルが好ましい。シリカゲルは顆粒
状、ビーズ状、タブレット状のものが市販されている
が、そのいずれもが使用可能である。[0012] Such a dry atmosphere is, for example, in the above-described gas-impermeable moisture-resistant container together with a deoxidizer.
The container can be formed by putting a desiccant and sealing the container. Examples of the desiccant that can be used include phosphorus pentoxide, calcium chloride, silica gel, calcium oxide, and the like, with silica gel being preferred. Silica gel is commercially available in the form of granules, beads, and tablets, and any of them can be used.
【００１３】また、脱酸素剤と乾燥剤とを混合して用い
てもよく、その混合物は、適宜、粉体、顆粒、錠剤等の
形状で用いられる。Further, the oxygen scavenger and the desiccant may be mixed and used, and the mixture is used in the form of powder, granules, tablets and the like as appropriate.
【００１４】乾燥剤、脱酸素剤及びそれらの混合物はア
カルボース又はアカルボース含有製剤に直接触れること
は好ましくなく、通常、通気性包装材料に包装したうえ
でアカルボース又はアカルボース含有製剤の包装容器に
封入される。It is not preferable that the desiccant, the oxygen absorber and the mixture thereof come into direct contact with the acarbose or the acarbose-containing preparation. Usually, the desiccant, the oxygen absorber and the mixture are packaged in a breathable packaging material and then enclosed in a packaging container of the acarbose or the acarbose-containing preparation. .
【００１５】アカルボース又はアカルボース含有製剤の
保存に使用される実質的に気体不透過性の耐湿容器とし
ては、酸素透過度が２０ml／m2・atm・24Hr 以下、特に
１０ml／m2・atm・24Hr （２５℃、６０％ＲＨ）以下の
ものが好ましい。さらにアカルボースの吸湿を防ぐた
め、該容器は、透湿度が１０ｇ／m2・24Hr以下、好まし
くは５ｇ／m2・24Hr以下（４０℃、９０％ ＲＨ ）であ
ることが好ましい。具体的には、例えば、鉄、アルミニ
ウム等の金属製の成形容器や缶；パッキン栓付きガラス
びん；ポリ塩化ビニリデン、ポリビニルアルコール、ナ
イロン等の素材からなる成形容器または袋；アルミニウ
ム箔を積層するか又はアルミニウム、酸化アルミニウム
もしくは珪素化合物を蒸着した各種プラスチックフィル
ムからなる成形容器または袋等が挙げられる。A substantially gas-impermeable moisture-resistant container used for storing acarbose or acarbose-containing preparations has an oxygen permeability of 20 ml / m 2 · atm · 24Hr or less, particularly 10 ml / m 2 · atm · 24Hr. (25 ° C., 60% RH) or less are preferred. Further, in order to prevent moisture absorption of acarbose, the container preferably has a moisture permeability of 10 g / m 2 · 24Hr or less, preferably 5 g / m 2 · 24Hr or less (40 ° C., 90% RH). Specifically, for example, a molded container or can made of metal such as iron or aluminum; a glass bottle with a packing stopper; a molded container or bag made of a material such as polyvinylidene chloride, polyvinyl alcohol, or nylon; Alternatively, a molded container or bag made of various plastic films on which aluminum, aluminum oxide, or a silicon compound is vapor-deposited may be used.
【００１６】しかして、本発明によれば、アカルボース
又はアカルボース製剤及び脱酸素手段、これらを収容す
る上記の如き実質的に気体不透過性の耐湿容器からなる
アカルボース又はアカルボース製剤の包装物が提供され
る。Thus, according to the present invention, there is provided a package of acarbose or an acarbose formulation comprising an acarbose or an acarbose formulation and a deoxygenating means, and a substantially gas-impermeable, moisture-resistant container as described above for accommodating the acarbose or the acarbose formulation. You.
【００１７】なお、アカルボース又はアカルボース製剤
はそのまま該容器に投入することができるが、予めＰＴ
Ｐ包装のような耐湿容器内に密封した後、さらに脱酸素
剤及び場合によりさらに乾燥剤と共に実質的に気体不透
過性の容器に保存するようにしてもよい。Acarbose or an acarbose preparation can be put into the container as it is.
After sealing in a moisture-resistant container such as a P-wrap, it may be stored in a substantially gas-impermeable container with additional oxygen scavenger and optionally further desiccant.
【００１８】以下、本発明を実施例により更に具体的に
説明する。Hereinafter, the present invention will be described more specifically with reference to examples.
【００１９】[0019]
実施例１ 室温、相対湿度約６０％の雰囲気のもとで、アカルボー
スを５０ｍｇ含有する錠剤（グルコバイ錠５０ｍｇ：バ
イエル薬品株式会社製）を、（１）単独で、（２）乾燥
剤と共に、（３）脱酸素剤と共に、又は（４）乾燥剤及
び脱酸素剤と共に、それぞれ２０錠づつ容量約６０ｍｌ
の褐色ガラス容器に密封し、４０℃で保存した。試験開
始１週間後、２週間後、４週間後及び１２週間後に、錠
剤の色調の変化を色差計（Micro Color：DR.LANGE社
製）で測定した。なお、乾燥剤としてはシリカゲルＰＷ
２０１０（山仁薬品株式会社製）を、脱酸素剤としてエ
ージレスＺ−２０ＰＫ（三菱ガス化学株式会社製）をそ
れぞれ用いた。結果を表１に示す。Example 1 Under an atmosphere at room temperature and a relative humidity of about 60%, a tablet containing 50 mg of acarbose (Glucobay tablet 50 mg: manufactured by Bayer Yakuhin Co., Ltd.) was used for (1) alone, (2) together with a desiccant, 3) 20 tablets each with oxygen scavenger or (4) desiccant and oxygen scavenger, about 60 ml in volume
And stored at 40 ° C. One week, two weeks, four weeks, and 12 weeks after the start of the test, the change in the color tone of the tablet was measured with a color difference meter (Micro Color: manufactured by DR. LANGE). As a desiccant, silica gel PW
2010 (manufactured by Yamahito Pharmaceutical Co., Ltd.) and Ageless Z-20PK (manufactured by Mitsubishi Gas Chemical Co., Ltd.) were used as oxygen scavengers, respectively. Table 1 shows the results.
【００２０】[0020]
【表１】 [Table 1]
【００２１】実施例２ 室温、相対湿度約６０％の雰囲気のもとで、アカルボー
スを５０ｍｇ含有する錠剤（グルコバイ錠５０ｍｇ：バ
イエル薬品株式会社製）を、（１）ＰＴＰ包装（ＣＰ
Ｐ）、（２）ＰＴＰ包装（ＣＰＰ）して乾燥剤と共に、
又は（３）ＰＴＰ包装して脱酸素剤と共に、それぞれ１
０錠づつアルミラミネートフィルム（ポリエステル１２
μｍ／ポリエチレン１３μｍ ／アルミ９μｍ ／ポリエ
チレン４０μｍ ）で密封包装し、６０℃で保存した。
試験開始１週間後、２週間後及び３週間後に、錠剤の色
調の変化を色差計（Micro Color：DR.LANGE社製）で測
定した。なお、乾燥剤としては塩化カルシウム（シート
状：株式会社アイディ製）を、脱酸素剤としてエージレ
スＺ−２０（三菱ガス化学株式会社製）をそれぞれ用い
た。結果を表２に示す。Example 2 A tablet containing 50 mg of acarbose (Glucobay tablet 50 mg: manufactured by Bayer Yakuhin, Ltd.) in an atmosphere at room temperature and a relative humidity of about 60% was packed in a (1) PTP package (CP
P), (2) PTP packaging (CPP) and desiccant,
Or (3) PTP-packed with oxygen scavenger, 1 each
0 tablets each aluminum laminated film (polyester 12
μm / polyethylene 13 μm / aluminum 9 μm / polyethylene 40 μm) and stored at 60 ° C.
One week, two weeks, and three weeks after the start of the test, the change in the color tone of the tablet was measured with a color difference meter (Micro Color: manufactured by DR. LANGE). In addition, calcium chloride (sheet form: manufactured by ID Corporation) was used as a desiccant, and Ageless Z-20 (manufactured by Mitsubishi Gas Chemical Co., Ltd.) was used as a deoxidizer. Table 2 shows the results.
【００２２】[0022]
【表２】 [Table 2]
【００２３】実施例３ ２０℃、相対湿度４５％の低湿ブース内で、ドラムホー
プ混合機（池田機械産業株式会社製）内に、アカルボー
ス３５０ｇ、結晶セルロース７７０ｇ、軽質無水ケイ酸
３．５ｇ及び水分量が６％以下に乾燥したトウモロコシ
デンプン７６０ｇを入れ１０分間混合し、さらにステア
リン酸マグネシウム７ｇを入れ５分間混合した。これを
ロータリー式打錠機（菊水製作所製コレクト１９Ｋ）を
用い、φ７ｍｍ、１３５ｍｇ／錠になるように打錠し、
アカルボースを２５ｍｇ含有する錠剤約１０，０００錠
を得た。Example 3 In a low humidity booth at 20 ° C. and a relative humidity of 45%, acarbose (350 g), crystalline cellulose (770 g), light anhydrous silicic acid (3.5 g) and water were placed in a drum hope mixer (manufactured by Ikeda Kikai Sangyo Co., Ltd.). 760 g of corn starch dried to an amount of 6% or less was added and mixed for 10 minutes, and then 7 g of magnesium stearate was added and mixed for 5 minutes. Using a rotary tableting machine (Collect 19K, manufactured by Kikusui Seisakusho), the tablet was compressed to a diameter of 7 mm and 135 mg / tablet.
About 10,000 tablets containing 25 mg of acarbose were obtained.
【００２４】室温、相対湿度約６０％の雰囲気のもと
で、この２５ｍｇ錠および市販の５０ｍｇ錠（バイエル
薬品株式会社製）のそれぞれの錠剤を、（１）単独で、
又は（２）脱酸素剤と共に、それぞれ２０錠づつ容量約
６０ｍｌの褐色ガラス容器に密封し、４０℃で保存し
た。試験開始１ヶ月後、２ヶ月後及び３ケ月後に、錠剤
の色調の変化を色差計（Micro Color：DR.LANGE社製）
で測定した。なお、脱酸素剤としてエージレスＳＡ−２
０（三菱ガス化学株式会社製）を用いた。結果を表３に
示す。Under an atmosphere at room temperature and a relative humidity of about 60%, each of the 25 mg tablet and a commercially available 50 mg tablet (manufactured by Bayer Yakuhin, Ltd.)
Alternatively, (2) together with a deoxidizer, 20 tablets each were sealed in a brown glass container having a capacity of about 60 ml and stored at 40 ° C. One month, two months, and three months after the start of the test, the change in the color tone of the tablet is measured using a color difference meter (Micro Color: manufactured by DR. LANGE).
Was measured. In addition, Ageless SA-2 is used as a deoxidizer.
0 (manufactured by Mitsubishi Gas Chemical Co., Ltd.). Table 3 shows the results.
【００２５】[0025]
【表３】 [Table 3]
【００２６】実施例４ ２０℃、相対湿度４５％の低湿ブース内で、ドラムホー
プ混合機（池田機械産業株式会社製）内に、アカルボー
ス７００ｇ、結晶セルロース４２０ｇ、軽質無水ケイ酸
３．５ｇ及び水分量が６％以下に乾燥したトウモロコシ
デンプン７６０ｇを入れ１０分間混合し、さらにステア
リン酸マグネシウム７ｇを入れ５分間混合した。これを
ロータリー式打錠機（菊水製作所製コレクト１９Ｋ）を
用い、φ７ｍｍ、１３５ｍｇ／錠になるように打錠し、
アカルボースを５０ｍｇ含有する錠剤約１０，０００錠
を得た。Example 4 In a low humidity booth at 20 ° C. and a relative humidity of 45%, 700 g of acarbose, 420 g of crystalline cellulose, 3.5 g of light anhydrous silicic acid and 3.5 g of water were placed in a drum hope mixer (made by Ikeda Kikai Sangyo Co., Ltd.). 760 g of corn starch dried to an amount of 6% or less was added and mixed for 10 minutes, and then 7 g of magnesium stearate was added and mixed for 5 minutes. This was tableted using a rotary tableting machine (Collect 19K, manufactured by Kikusui Seisakusho) so as to have a diameter of φ7 mm and 135 mg / tablet.
About 10,000 tablets containing 50 mg of acarbose were obtained.
【００２７】この５０ｍｇ錠を２０錠づつ、相対湿度約
６０％の雰囲気下に以下の容器に入れて密封し、４０℃
で２ケ月間保存した。Each of the 50 mg tablets is sealed in a container below in an atmosphere at a relative humidity of about 60% at a temperature of about 40%.
For 2 months.
【００２８】（１） 容量約６０ｍｌの褐色ガラス容器 （２） 容器内の空気を窒素置換した容量約６０ｍｌの
褐色ガラス容器 （３） 真空アルミラミネートフィルム容器 （４） 脱酸素剤（ＳＤ−１００：日本曹達株式会社
製）を同封したアルミラミネートフィルム容器 保存開始１ケ月後及び２ケ月後に、錠剤の色調の変化を
色差計（Micro Color：DR.LANGE 社製）で測定した。結
果を表４に示す。(1) Brown glass container with a capacity of about 60 ml (2) Brown glass container with a capacity of about 60 ml with the air in the container replaced with nitrogen (3) Vacuum aluminum laminated film container (4) Oxygen absorber (SD-100: One month and two months after the start of storage, the change in the color tone of the tablets was measured with a color difference meter (Micro Color: manufactured by DR. LANGE) one month after the start of storage and two months after storage. Table 4 shows the results.
【００２９】[0029]
【表４】 [Table 4]
Claims (6)
を実質的に酸素を含まない雰囲気中に保持することを特
徴とするアカルボース又はアカルボース含有製剤の保存
方法。1. A method for preserving acarbose or an acarbose-containing preparation, comprising maintaining the acarbose or the acarbose-containing preparation in an atmosphere substantially free of oxygen.
を、酸素が実質的に除去された実質的に気体不透過性の
耐湿容器内に密封することを特徴とするアカルボース又
はアカルボース含有製剤の保存方法。2. A method for preserving acarbose or an acarbose-containing preparation, comprising sealing the acarbose or the acarbose-containing preparation in a substantially gas-impermeable, moisture-proof container from which oxygen has been substantially removed.
を、脱酸素剤と共に実質的に気体不透過性の耐湿容器内
に密封して保存することを特徴とするアカルボース又は
アカルボース含有製剤の保存方法。3. A method for storing acarbose or an acarbose-containing preparation, wherein the acarbose or the acarbose-containing preparation is sealed and stored in a substantially gas-impermeable, moisture-proof container together with an oxygen scavenger.
を耐湿容器内に密封し、これをさらに脱酸素剤と共に実
質的に気体不透過性の容器内に保存することを特徴とす
るアカルボース又はアカルボース含有製剤の保存方法。4. Storage of acarbose or acarbose-containing preparation, characterized in that the acarbose or acarbose-containing preparation is sealed in a moisture-proof container and further stored in a substantially gas-impermeable container together with a deoxidizer. Method.
度２０％以下及び酸素濃度１％以下であることを特徴と
する請求項１〜４のいずれかに記載の方法。5. The method according to claim 1, wherein the atmosphere in the gas impermeable container has a relative humidity of 20% or less and an oxygen concentration of 1% or less.
及び脱酸素手段、並びにこれらを収容する実質的に気体
不透過性の耐湿密封容器からなるアカルボース又はアカ
ルボース含有製剤の包装物。6. A package of acarbose or an acarbose-containing preparation comprising an acarbose or an acarbose-containing preparation and a deoxygenation means, and a substantially gas-impermeable, moisture-tight container containing the acarbose or acarbose-containing preparation.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9177833A JPH10182687A (en) | 1996-10-21 | 1997-06-19 | Stabilization of storage of acarbose |
| EP97117551A EP0837069A1 (en) | 1996-10-21 | 1997-10-10 | Storage-stabilization method of acarbose |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8-297062 | 1996-10-21 | ||
| JP29706296 | 1996-10-21 | ||
| JP9177833A JPH10182687A (en) | 1996-10-21 | 1997-06-19 | Stabilization of storage of acarbose |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH10182687A true JPH10182687A (en) | 1998-07-07 |
Family
ID=26498229
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9177833A Pending JPH10182687A (en) | 1996-10-21 | 1997-06-19 | Stabilization of storage of acarbose |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP0837069A1 (en) |
| JP (1) | JPH10182687A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006342126A (en) * | 2005-06-10 | 2006-12-21 | Nichi-Iko Pharmaceutical Co Ltd | Acarbose-containing tablet excellent in time stability |
| JPWO2020004541A1 (en) * | 2018-06-27 | 2021-07-08 | 中外製薬株式会社 | A pharmaceutical composition containing an oil dispersion containing ED-71 and its epoxy body in fats and oils. |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19823831A1 (en) * | 1998-05-28 | 1999-12-02 | Probiodrug Ges Fuer Arzneim | New pharmaceutical use of isoleucyl thiazolidide and its salts |
| AU2000250960A1 (en) † | 2000-06-09 | 2001-12-17 | Lek Pharmaceuticals D.D. | Stable pharmaceutical product and formulation |
| EP1243524A3 (en) | 2001-03-16 | 2004-04-07 | Pfizer Products Inc. | Pharmaceutical kit for oxygen-sensitive drugs |
| JP4346311B2 (en) * | 2001-04-27 | 2009-10-21 | 京都薬品工業株式会社 | How to store effervescent suppositories |
| PE20130403A1 (en) * | 2010-04-27 | 2013-04-13 | Bayer Ip Gmbh | ORAL DISINTEGRATION TABLET CONTAINING ACARBOSE |
| CN103505441A (en) * | 2012-06-29 | 2014-01-15 | 北京韩美药品有限公司 | Oral solid preparation containing biguanides and acarbose and preparation method thereof |
| BR112015021586B1 (en) | 2013-03-14 | 2023-01-31 | Fresenius Kabi Deutschland Gmbh | INJECTABLE PHARMACEUTICAL MORPHINE FORMULATION AND KIT |
| WO2014140097A1 (en) | 2013-03-14 | 2014-09-18 | Becton Dickinson France S.A.S. | Packaging system for oxygen-sensitive drugs |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3134591A1 (en) * | 1981-09-01 | 1983-03-10 | Bayer Ag, 5090 Leverkusen | NEW MEDICINE PREPARATIONS FOR GLYCOSIDE HYDROLASE INHIBITORS |
| JPH0739340A (en) * | 1993-08-04 | 1995-02-10 | Shozo Shimizu | Method for preventing discoloration of foliage of japanese horseradish due to high-temperature heat sterilization |
-
1997
- 1997-06-19 JP JP9177833A patent/JPH10182687A/en active Pending
- 1997-10-10 EP EP97117551A patent/EP0837069A1/en not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006342126A (en) * | 2005-06-10 | 2006-12-21 | Nichi-Iko Pharmaceutical Co Ltd | Acarbose-containing tablet excellent in time stability |
| JPWO2020004541A1 (en) * | 2018-06-27 | 2021-07-08 | 中外製薬株式会社 | A pharmaceutical composition containing an oil dispersion containing ED-71 and its epoxy body in fats and oils. |
| JP2022065053A (en) * | 2018-06-27 | 2022-04-26 | 中外製薬株式会社 | Pharmaceutical composition comprising oil component dispersion that contains ed-71 and epoxy form thereof in fat/oil |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0837069A1 (en) | 1998-04-22 |
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